The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population.

Neuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
Neurogenetics (Impact Factor: 3.58). 09/2008; 9(4):271-6. DOI: 10.1007/s10048-008-0140-6
Source: PubMed

ABSTRACT The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29-3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson's disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson's disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] approximately 4%) and Gly2385Arg variants (PAR approximately 6%) yields a total PAR of approximately 10%.

  • Source
    Journal of neurology, neurosurgery, and psychiatry 10/2011; 82(10):1179-80. · 4.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In 2004 it was first shown that mutations in LRRK2 can cause Parkinson's disease. This initial discovery was quickly followed by the observation that a single particular mutation is a relatively common cause of Parkinson's disease across varied populations. Further genetic investigation has revealed a variety of genetic ties to Parkinson's disease across this gene. These include common alleles with quite broad effects on risk, likely through both alterations at the protein sequence level, and in the context of expression. A great deal of functional characterization of LRRK2 and disease-causing mutations in this protein has occurred over the last 9 years, and considerable progress has been made. Particular attention has been paid to the kinase activity of LRRK2 as a therapeutic target, and while it is no means certain that this is viable target it is likely that this hypothesis will be tested in clinical trials sooner rather than later. We believe that the future goals for LRRK2 research are, while challenging, relatively clear and that the next 10 years of research promises to be perhaps more exciting than the last.
    Journal of Parkinson's disease. 01/2013; 3(2):85-103.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The G2385R and R1628P polymorphisms of the leucine-rich repeat kinase 2 (LRRK2) gene have been reported to be associated with Parkinson's disease (PD), but no data are available on Han-Chinese population of south-eastern China. This study aimed to investigate whether G2385R and R1628P variants are associated with sporadic PD in this population. Total 1,060 subjects were enrolled; including 550 unrelated healthy controls and 510 patients with sporadic PD. Genotyping of polymorphisms was performed by PCR-restriction fragment length polymorphism analysis. All variant samples were sequenced for further confirmation. The results showed that the A allele of the G2385R variant was significantly enriched in sporadic PD patient group (4.8 %) when compared with control group [1.1 %; odds ratio (OR) 4.58, 95 % confidence interval (CI) 2.42-8.65, P < 0.01]. However, no significant difference in the frequency of the C allele of R1628P polymorphism variant was observed between cases and controls (2.8 vs. 1.7 %, OR 1.67, 95 % CI 0.93-2.99, P = 0.08). In conclusion, this study provides the first evidence that G2385R polymorphism is a risk factor for sporadic PD in Han-Chinese population of south-eastern China.
    Neurological Sciences 04/2013; · 1.41 Impact Factor

Full-text (2 Sources)

Available from
May 29, 2014